CN109248147A - A kind of solubility Ormetoprim solid dispersions and preparation method thereof - Google Patents
A kind of solubility Ormetoprim solid dispersions and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a kind of soluble Ormetoprim solid dispersions and preparation method thereof, the solubility Ormetoprim solid dispersions, including Ormetoprim or its salt, solubleness carrier, Ormetoprim or its salt can be increased and the mass ratio of solubleness carrier can be increased as 1:3~1:12；A kind of preparation method of solubility Ormetoprim solid dispersions, the following steps are included: 1) can increase solubleness carrier according to formula ratio and be melted at 60~90 DEG C, it is rear that Ormetoprim or its salt is added, 80~120 DEG C are warming up to, stirring to the transparent state of molten liquid；2) molten liquid of pellucidity is poured into the container of pre-cooling, is crushed after cooling and solidifying, soluble Ormetoprim solid dispersions can be obtained.It is an advantage of the invention that solubleness carrier can be increased due to being added in Ormetoprim or its salt, the dissolubility of Ormetoprim can be improved.The above method, due to that by Ormetoprim or its salt and can increase solubleness carrier progress mixed melting using fusion method, dispersibility is preferably.
Description
Technical field
The present invention relates to Ormetoprim fields, more particularly to a kind of soluble Ormetoprim solid dispersions and its preparation
Method.
Background technique
Ormetoprim (OMP) is a kind of efficient Trimethoprim of veterinary drug special broad-spectrum, is mainly used as sulfamido antibacterial agent
Synergist, prevent and treat the bacterium infection of livestock and poultry, foreign countries common are the premix of Ormetoprim and sulfadimethoxine
Agent and tablet, but due to Ormetoprim almost insoluble, absorption difference in water itself, spice is irregular or diet can all influence drug effect
Play, if being made into soluble form, apply to drinking water administration, then dispensing can be made convenient, also can be improved drug absorption and
It utilizes.Generally, Ormetoprim can be with organic acid or inorganic acids, and to improve water solubility, but the soluble-salt of this form exists
It when being used in combination with soluble sulfa drug (usually alkaline sodium salt), due to antagonism, can influence each other, cause the molten of the two
Xie Du declines, and precipitating can be generated when serious, influences medication effect.
Summary of the invention
Goal of the invention: in view of the above-mentioned problems, an object of the present invention is to provide a kind of soluble Ormetoprim solid point
Granular media, to solve to generate precipitating, influence the technical issues of medication effect.
The second object of the present invention is to provide a kind of preparation method of soluble Ormetoprim solid dispersions.
Technical solution:
A kind of solubility Ormetoprim solid dispersions, including Ormetoprim or its salt, solubleness carrier, Ormetoprim can be increased
Or its salt is 1:3~1:12 with the mass ratio that can increase solubleness carrier.It is carried since solubilising being added in Ormetoprim or its salt
The dissolubility of Ormetoprim can be improved in body, and soluble Ormetoprim solid dispersions are used in combination with soluble sulfa drug
When, antagonism will not be generated, the solubility of the two will not be reduced, no precipitating generates, and will not influence medication effect.
It is PEG, Poloxamer, nonylphenol polyoxyethylene ether or 12 that solubleness carrier can be increased in one of the embodiments,
Alkanol polyoxyethylene ether.
It is polyvinylpyrrolidone or hypromellose that solubleness carrier can be increased in one of the embodiments,.
Ormetoprim salt is Ormetoprim hydrochloride, Ormetoprim acetate, Ormetoprim in one of the embodiments,
Lactate or Ormetoprim amino-acid salt.
A kind of preparation method of solubility Ormetoprim solid dispersions, comprising the following steps:
1) according to formula ratio, solubleness carrier can be increased and melted at 60~90 DEG C, it is rear that Ormetoprim or its salt, heating is added
To 80~120 DEG C, stirring to the transparent state of molten liquid；
2) molten liquid of pellucidity is poured into the container of pre-cooling, is crushed after cooling and solidifying, soluble Austria can be obtained
Mei Pulin solid dispersions.The above method, due to being mixed Ormetoprim or its salt with solubleness carrier can be increased using fusion method
Melting is closed, the two is uniformly mixed, dispersibility preferably, can effectively improve Ormetoprim or the solubility of its salt.
A kind of preparation method of solubility Ormetoprim solid dispersions, comprising the following steps: according to formula ratio, by Aomei
It general woods or its salt and solubleness carrier can be increased all is added to 100~300mL alcohol solution, 2~6h is stirred at 70~90 DEG C, is obtained
Mixed liquor is concentrated by evaporation by mixed liquor, is precipitated crystal, and is filtered, is dried, and soluble Ormetoprim solid dispersions can be obtained.
The above method mixes the two due to that by Ormetoprim or its salt and can increase solubleness carrier progress mixed melting using solvent method
Uniformly, dispersibility preferably, can effectively improve Ormetoprim or the solubility of its salt.
In one of the embodiments, in alcohol solution, the volume ratio of alcohols solvent and water is 1:1~1:4.
Alcohols solvent is at least one of methanol, ethyl alcohol, propyl alcohol and butanol in one of the embodiments,.
A kind of preparation method of solubility Ormetoprim solid dispersions, comprising the following steps: according to formula ratio, by Aomei
General woods or its salt are mixed with that can increase solubleness carrier, are obtained mixture, 2~4h of ball mill grinding mixture are used afterwards, at 60~90 DEG C
3~6h of lower vacuum drying, can be obtained soluble Ormetoprim solid dispersions.The above method, due to using polishing will be difficult to understand
It Mei Pulin or its salt and solubleness carrier can be increased carries out mixed melting, both make to be uniformly mixed, dispersibility preferably, can effectively improve
The solubility of Ormetoprim or its salt.
The utility model has the advantages that compared with prior art, the invention has the advantages that
1) above-mentioned soluble Ormetoprim solid dispersions, carry since solubilising being added in Ormetoprim or its salt
The dissolubility of Ormetoprim can be improved in body, and soluble Ormetoprim solid dispersions are used in combination with soluble sulfa drug
When, antagonism will not be generated, the solubility of the two will not be reduced, no precipitating generates, and will not influence medication effect.
2) preparation method of above-mentioned soluble Ormetoprim solid dispersions, due to using polishing, solvent method or grinding
Method by Ormetoprim or its salt and can increase solubleness carrier progress mixed melting, be uniformly mixed the two, dispersibility preferably, can
Effectively improve Ormetoprim or the solubility of its salt.
Specific embodiment
Embodiment 1
A kind of solubility Ormetoprim solid dispersions, including Ormetoprim and PEG6000, wherein Ormetoprim with
The mass ratio of PEG6000 is 1:3.
A kind of preparation method of solubility Ormetoprim solid dispersions, comprising the following steps:
1) according to formula ratio, the PEG6000 of 6.0g is melted at 80 DEG C, the rear Ormetoprim that 2.0g is added is warming up to
120 DEG C, stirring to the transparent state of molten liquid；
2) molten liquid of pellucidity is poured into the container of pre-cooling, is crushed after cooling and solidifying, crossed 80 meshes, can be obtained
Soluble Ormetoprim solid dispersions.
Embodiment 2
A kind of solubility Ormetoprim solid dispersions, including Ormetoprim and nonylphenol polyoxyethylene ether, wherein Aomei
Pu Lin and the mass ratio of nonylphenol polyoxyethylene ether are 1:5.
A kind of preparation method of solubility Ormetoprim solid dispersions, comprising the following steps:
1) according to formula ratio, the nonylphenol polyoxyethylene ether of 10.0g is melted at 60 DEG C, the rear Aomei that 2.0g is added is general
Woods is warming up to 110 DEG C, stirring to the transparent state of molten liquid；
2) molten liquid of pellucidity is poured into the container of pre-cooling, is crushed after cooling and solidifying, crossed 80 meshes, can be obtained
Soluble Ormetoprim solid dispersions.
Embodiment 3
A kind of solubility Ormetoprim solid dispersions, including Ormetoprim and PEG6000, wherein Ormetoprim with
The mass ratio of PEG6000 is 1:7.
A kind of preparation method of solubility Ormetoprim solid dispersions, comprising the following steps:
1) according to formula ratio, the PEG6000 of 14.0g is melted at 90 DEG C, the rear Ormetoprim that 2.0g is added is warming up to
100 DEG C, stirring to the transparent state of molten liquid；
2) molten liquid of pellucidity is poured into the container of pre-cooling, is crushed after cooling and solidifying, crossed 80 meshes, can be obtained
Soluble Ormetoprim solid dispersions.
Embodiment 4
A kind of solubility Ormetoprim solid dispersions, including Ormetoprim and dodecanol polyoxyethylene ether, wherein difficult to understand
Mei Pulin and the mass ratio of dodecanol polyoxyethylene ether are 1:9.
A kind of preparation method of solubility Ormetoprim solid dispersions, comprising the following steps:
1) according to formula ratio, the dodecanol polyoxyethylene ether of 18.0g is melted at 70 DEG C, the rear Aomei that 2.0g is added
Pu Lin is warming up to 90 DEG C, stirring to the transparent state of molten liquid；
2) molten liquid of pellucidity is poured into the container of pre-cooling, is crushed after cooling and solidifying, crossed 80 meshes, can be obtained
Soluble Ormetoprim solid dispersions.
Embodiment 5
A kind of solubility Ormetoprim solid dispersions, including Ormetoprim and Poloxamer, wherein Ormetoprim and pa
The mass ratio of Luo Shamu is 1:10.
A kind of preparation method of solubility Ormetoprim solid dispersions, comprising the following steps:
1) according to formula ratio, the Poloxamer of 20.0g is melted at 80 DEG C, the rear Ormetoprim that 2.0g is added continues
Kept for 80 DEG C, stirring to the transparent state of molten liquid；
2) molten liquid of pellucidity is poured into the container of pre-cooling, is crushed after cooling and solidifying, crossed 80 meshes, can be obtained
Soluble Ormetoprim solid dispersions.
Embodiment 6
A kind of solubility Ormetoprim solid dispersions, including Ormetoprim and PEG12000, wherein Ormetoprim with
The mass ratio of PEG12000 is 1:12.
A kind of preparation method of solubility Ormetoprim solid dispersions, comprising the following steps:
1) according to formula ratio, the PEG12000 of 24.0g is melted at 80 DEG C, the rear Ormetoprim that 2.0g is added, heating
To 90 DEG C, stirring to the transparent state of molten liquid；
2) molten liquid of pellucidity is poured into the container of pre-cooling, is crushed after cooling and solidifying, crossed 80 meshes, can be obtained
Soluble Ormetoprim solid dispersions.
Embodiment 7
A kind of solubility Ormetoprim solid dispersions, including Ormetoprim and PEG6000, wherein Ormetoprim with
The mass ratio of PEG6000 is 1:8.
A kind of preparation method of solubility Ormetoprim solid dispersions, comprising the following steps:
1) according to formula ratio, the nonylphenol polyoxyethylene ether of 16.0g is melted at 80 DEG C, the rear Aomei that 2.0g is added is general
Woods or its salt are warming up to 110 DEG C, stirring to the transparent state of molten liquid；
2) molten liquid of pellucidity is poured into the container of pre-cooling, is crushed after cooling and solidifying, crossed 80 meshes, can be obtained
Soluble Ormetoprim solid dispersions.
Embodiment 8
A kind of solubility Ormetoprim solid dispersions, including Ormetoprim and polyvinylpyrrolidone K-15, wherein difficult to understand
The mass ratio of Mei Pulin and polyvinylpyrrolidone K-15 is 1:3.
A kind of preparation method of solubility Ormetoprim solid dispersions, comprising the following steps: according to formula ratio, by 2.0g
Ormetoprim and the polyvinylpyrrolidone K-15 of 6.0g be all added to 200mL alcohol solution, stir 4h at 80 DEG C, obtain
Mixed liquor is concentrated by evaporation by mixed liquor, is precipitated crystal, and filtering, filter cake is dried in vacuo 4h at 60 DEG C, and soluble Austria can be obtained
Mei Pulin solid dispersions.
Wherein, in alcohol solution, the volume ratio of ethyl alcohol and water is 1:1.
Embodiment 9
A kind of solubility Ormetoprim solid dispersions, including Ormetoprim and hypromellose, wherein Aomei is general
The mass ratio of woods and hypromellose is 1:4.
A kind of preparation method of solubility Ormetoprim solid dispersions, comprising the following steps: according to formula ratio, by 2.0g
Ormetoprim and the hypromellose of 8.0g be all added to 200mL alcohol solution, stir 8h at 70 DEG C, mixed
Mixed liquor is concentrated by evaporation by liquid, is precipitated crystal, and filtering, filter cake is dried in vacuo 6h at 50 DEG C, it is general that soluble Aomei can be obtained
Woods solid dispersions.
Wherein, in alcohol solution, the volume ratio of ethyl alcohol and water is 1:2.
Embodiment 10
A kind of solubility Ormetoprim solid dispersions, including Ormetoprim and PVP K-30, wherein difficult to understand
The mass ratio of Mei Pulin and PVP K-30 is 1:6.
A kind of preparation method of solubility Ormetoprim solid dispersions, comprising the following steps: according to formula ratio, by 2.0g
Ormetoprim and the PVP K-30 of 12.0g be all added to 250mL alcohol solution, stir 4h at 85 DEG C, obtain
To mixed liquor, mixed liquor is concentrated by evaporation, is precipitated crystal, is filtered, filter cake is dried in vacuo 4h at 60 DEG C, solubility can be obtained
Ormetoprim solid dispersions.
Wherein, in alcohol solution, the volume ratio of ethyl alcohol and water is 1:3.
Embodiment 11
A kind of solubility Ormetoprim solid dispersions, including Ormetoprim and PVP K-30, wherein difficult to understand
The mass ratio of Mei Pulin and PVP K-30 is 1:8.
A kind of preparation method of solubility Ormetoprim solid dispersions, comprising the following steps: according to formula ratio, by 2.0g
Ormetoprim and the PVP K-30 of 16.0g be all added to 300mL alcohol solution, stir 5h at 75 DEG C, obtain
To mixed liquor, mixed liquor is concentrated by evaporation, is precipitated crystal, is filtered, filter cake is dried in vacuo 4h at 80 DEG C, solubility can be obtained
Ormetoprim solid dispersions.
Wherein, in alcohol solution, the volume ratio of ethyl alcohol and water is 1:1.
Embodiment 12
A kind of solubility Ormetoprim solid dispersions, including Ormetoprim and polyvinylpyrrolidone K-15, wherein difficult to understand
The mass ratio of Mei Pulin and polyvinylpyrrolidone K-15 is 1:4.
A kind of preparation method of solubility Ormetoprim solid dispersions, comprising the following steps: according to formula ratio, by 2.0g
Ormetoprim and the polyvinylpyrrolidone K-15 of 8.0g be all added to 100mL alcohol solution, stir 2h at 90 DEG C, obtain
Mixed liquor is concentrated by evaporation by mixed liquor, is precipitated crystal, and filtering, filter cake is dried in vacuo 5h at 70 DEG C, and soluble Austria can be obtained
Mei Pulin solid dispersions.
Wherein, in alcohol solution, the volume ratio of ethyl alcohol and water is 1:4.
Embodiment 13
A kind of solubility Ormetoprim solid dispersions, including Ormetoprim and PVP K-30, wherein difficult to understand
The mass ratio of Mei Pulin and PVP K-30 is 1:6.
A kind of preparation method of solubility Ormetoprim solid dispersions, comprising the following steps: according to formula ratio, by 2.0g
Ormetoprim and the PVP K-30 of 12.0g be all added to 150mL alcohol solution, stir 4h at 80 DEG C, obtain
To mixed liquor, mixed liquor is concentrated by evaporation, is precipitated crystal, is filtered, filter cake is dried in vacuo 6h at 40 DEG C, solubility can be obtained
Ormetoprim solid dispersions.
Wherein, in alcohol solution, the volume ratio of propyl alcohol and water is 1:1.
Embodiment 14
A kind of solubility Ormetoprim solid dispersions, including Ormetoprim lactate and PVP K-30,
Wherein, the mass ratio of Ormetoprim lactate and PVP K-30 is 1:3.
A kind of preparation method of solubility Ormetoprim solid dispersions, comprising the following steps:, will according to formula ratio
20.0g Ormetoprim lactate and 60.0g PVP K-30 mix, and obtain mixture, after it is mixed with ball mill grinding
Object 3h is closed, 6h is dried in vacuo at 60 DEG C, soluble Ormetoprim solid dispersions can be obtained.
Embodiment 15
A kind of solubility Ormetoprim solid dispersions, including Ormetoprim and polyvinylpyrrolidone K-15, wherein difficult to understand
The mass ratio of Mei Pulin and polyvinylpyrrolidone K-15 is 1:5.
A kind of preparation method of solubility Ormetoprim solid dispersions, comprising the following steps:, will according to formula ratio
20.0g Ormetoprim and 100.0g polyvinylpyrrolidone K-15 are mixed, and obtain mixture, use ball mill grinding mixture afterwards
3h is dried in vacuo 4h at 60 DEG C, and soluble Ormetoprim solid dispersions can be obtained.
Embodiment 16
A kind of solubility Ormetoprim solid dispersions, including Ormetoprim and hypromellose, wherein Aomei is general
The mass ratio of woods and hypromellose is 1:8.
A kind of preparation method of solubility Ormetoprim solid dispersions, comprising the following steps:, will according to formula ratio
20.0g Ormetoprim and 160.0g hypromellose mix, and obtain mixture, use ball mill grinding mixture 3h afterwards,
It is dried in vacuo 3h at 90 DEG C, soluble Ormetoprim solid dispersions can be obtained.
Embodiment 17
A kind of solubility Ormetoprim solid dispersions, including Ormetoprim lactate and PVP K-30,
Wherein, the mass ratio of Ormetoprim and PVP K-30 is 1:5.
A kind of preparation method of solubility Ormetoprim solid dispersions, comprising the following steps:, will according to formula ratio
20.0g Ormetoprim lactate and 100.0g PVP K-30 mix, and obtain mixture, after it is mixed with ball mill grinding
Object 3h is closed, 6h is dried in vacuo at 60 DEG C, soluble Ormetoprim solid dispersions can be obtained.
Embodiment 18
A kind of solubility Ormetoprim solid dispersions, including Ormetoprim and PVP K-30, wherein difficult to understand
The mass ratio of Mei Pulin and PVP K-30 is 1:12.
A kind of preparation method of solubility Ormetoprim solid dispersions, comprising the following steps:, will according to formula ratio
20.0g Ormetoprim and 240.0g PVP K-30 mix, and obtain mixture, use ball mill grinding mixture afterwards
3h is dried in vacuo 4h at 70 DEG C, and soluble Ormetoprim solid dispersions can be obtained.
Soluble test
Test group 1: weighing the soluble Ormetoprim solid dispersions that 0.45g embodiment 7 obtains, (wherein Ormetoprim contains
Measure 0.05g), 0.20g sodium sulfadiazine, the two is respectively placed in conical flask, in backward conical flask be added 100mL water, shaking
Or stirring 30min, the mixture situation after 30min, 6h, 12h is observed respectively.
Test group 2: soluble Ormetoprim solid dispersions (the wherein Ormetoprim that 0.35g embodiment 10 obtains is weighed
Content 0.05g), 0.20g sodium sulfadiazine, the two is respectively placed in conical flask, in backward conical flask be added 100mL water, vibration
30min is shaken or stirred, observes the mixture situation after 30min, 6h, 12h respectively.
Test group 3: soluble Ormetoprim solid dispersions (the wherein Ormetoprim that 0.35g embodiment 13 obtains is weighed
Content 0.05g), 0.20g sodium sulfadiazine, the two is respectively placed in conical flask, in backward conical flask be added 100mL water, vibration
30min is shaken or stirred, observes the mixture situation after 30min, 6h, 12h respectively.
Test group 4: soluble Ormetoprim solid dispersions (the wherein Ormetoprim that 0.40g embodiment 17 obtains is weighed
Content 0.05g), 0.20g sodium sulfadiazine, the two is respectively placed in conical flask, in backward conical flask be added 100mL water, vibration
30min is shaken or stirred, observes the mixture situation after 30min, 6h, 12h respectively.
Control group 1: the Ormetoprim and 0.20g sodium sulfadiazine for weighing 0.05g are respectively placed in conical flask, backward taper
100mL water, shaking or stirring 30min are added in bottle, observes the mixture situation after 30min, 6h, 12h respectively.
Control group 2: the Ormetoprim lactate and 0.20g sodium sulfadiazine for weighing 0.05g are respectively placed in conical flask, after
100mL water, shaking or stirring 30min are added into conical flask, observes the mixture situation after 30min, 6h, 12h respectively.
Control group 3: PEG6000 the and 0.20g sodium sulfadiazine of the Ormetoprim, 0.30g that weigh 0.05g is respectively placed in cone
In shape bottle, 100mL water, shaking or stirring 30min are added in backward conical flask, observes the mixture after 30min, 6h, 12h respectively
Situation.
Control group 4: the Ormetoprim of 0.05g, the PVP K-30 of 0.30g and 0.20g sulphadiazine are weighed
Sodium is respectively placed in conical flask, in backward conical flask be added 100mL water, shaking or stirring 30min, respectively observe 30min, 6h,
Mixture situation after 12h.The solubility test of test group 1~4 and control group 1~4 is observed, the results are shown in Table 1.
The solubility test comparing result of 1 test group 1~4 of table and control group 1~4
As shown in Table 1, the soluble Ormetoprim solid dispersions Yu sodium sulfadiazine of test group 1~4 of the invention are mixed
After merging dissolution, is still generated without precipitating after the long period, illustrate soluble Ormetoprim solid dispersions of the invention
Both it is soluble preferable, and matched with sodium sulfadiazine when using without antagonism, the compatibility of the two is higher, do not reduce
Solubility is conducive to pharmaceutically-active smooth performance.
Assay
Use chromatographic column for Diamonsil C18 column (200mm × 4.6mm, 5 μm), mobile phase is methanol: 0.02mol/L
Potassium dihydrogen phosphate=30:70, flow velocity 1.0mL/min, column temperature are 25 DEG C, and Detection wavelength is 280 μm, and mobile phase is as sample
Diluent, sample volume l0 μ L.
Sodium sulfadiazine reference substance is taken, precision weighing adds mobile phase that the sodium sulfadiazine for containing 50 μ g/mL in every 1mL is made
Reference substance solution；Ormetoprim reference substance is taken, precision weighing adds mobile phase that the Ormetoprim pair for containing 50 μ g/mL in every 1mL is made
According to product solution.
The solution for taking test group 1~4 and control group 1~4 to obtain in 30min, 6h, 12h respectively, with 0.45 μm of micro- air filter
Film filtering, is diluted with mobile phase 1:20, and precision measures 10 μ L injecting chromatographs, records chromatogram.By external standard method with peak area point
Not Ji Suan sodium sulfadiazine and Ormetoprim content, and converse actual content in proportion, the results are shown in Table 2.
2 solubility test sodium sulfadiazine of table and Ormetoprim assay table (g/100mL)
As shown in Table 2, soluble Ormetoprim solid dispersions of the invention, can obviously increase the dissolution of Ormetoprim
Property, keep the compatibility of Ormetoprim and sodium sulfadiazine preferable, and Ormetoprim, sodium sulfadiazine contain in the solution of practical measurement
Amount is close with theoretical value, and Ormetoprim, sulphadiazine sodium content are significantly lower than theoretical value, specification in 1~4 solution of control group
Soluble Ormetoprim solid dispersions solubilization of the invention is obvious, while being changed with the compatibility of sodium sulfadiazine
It is kind, it can be compounded with antimicrobials such as sulfa drugs, the water soluble preparations such as pulvis, tablet are made, can guarantee medication effect.
Claims (9)
1. a kind of solubility Ormetoprim solid dispersions, which is characterized in that carried including Ormetoprim or its salt, solubilising
Body, Ormetoprim or its salt are 1:3~1:12 with the mass ratio that can increase solubleness carrier.
2. a kind of soluble Ormetoprim solid dispersions according to claim 1, which is characterized in that solubleness carrier can be increased
For PEG, Poloxamer, nonylphenol polyoxyethylene ether or dodecanol polyoxyethylene ether.
3. a kind of soluble Ormetoprim solid dispersions according to claim 1, which is characterized in that solubleness carrier can be increased
For polyvinylpyrrolidone or hypromellose.
4. a kind of soluble Ormetoprim solid dispersions according to claim 1, which is characterized in that Ormetoprim salt is
Ormetoprim hydrochloride, Ormetoprim acetate, Ormetoprim lactate or Ormetoprim amino-acid salt.
5. a kind of preparation method of soluble Ormetoprim solid dispersions according to claim 2, which is characterized in that including with
Lower step:
1) according to formula ratio, solubleness carrier can be increased and melted at 60~90 DEG C, it is rear that Ormetoprim or its salt is added, it is warming up to 80
~120 DEG C, stirring to the transparent state of molten liquid；
2) molten liquid of pellucidity is poured into the container of pre-cooling, is crushed after cooling and solidifying, it is general that soluble Aomei can be obtained
Woods solid dispersions.
6. a kind of preparation method of soluble Ormetoprim solid dispersions according to claim 1, which is characterized in that including with
Lower step: according to formula ratio, by Ormetoprim or its salt and can increase solubleness carrier and be all added to 100~300mL alcohol solution,
2~6h is stirred at 70~90 DEG C, obtains mixed liquor, mixed liquor is concentrated by evaporation, precipitate crystal, filter, dry, can be obtained can
Dissolubility Ormetoprim solid dispersions.
7. a kind of preparation method of soluble Ormetoprim solid dispersions according to claim 6, which is characterized in that alcohol
In aqueous solution, the volume ratio of alcohols solvent and water is 1:1~1:4.
8. a kind of preparation method of soluble Ormetoprim solid dispersions according to claim 7, which is characterized in that alcohol
Class solvent is at least one of methanol, ethyl alcohol, propyl alcohol and butanol.
9. a kind of preparation method of soluble Ormetoprim solid dispersions according to claim 1, which is characterized in that including with
Lower step: according to formula ratio, by Ormetoprim or its salt and can increase solubleness carrier and mix, obtain mixture, after ground with ball mill
2~4h of mixture is ground, 3~6h is dried in vacuo at 60~90 DEG C, soluble Ormetoprim solid dispersions can be obtained.
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